A rise in cytosolic Ca2+ is used as a key signalling messenger in eukaryotic cells. The Ca2+ signal drives life and death and controls myriad responses in between. Inherent in the use of such a multifarious signal is the danger of disease, arising from dysregulated Ca2+ signalling. One ancient, highly conserved and widespread Ca2+ entry pathway is the store-operated Ca2+ release-activated Ca2+ (CRAC) channel. Mutations in STIM1 and ORAI1, the genes that encode the functional channel, are tightly linked to a CRAC channelopathy in humans, which encompasses severe combined immune deficiency, myopathy and anhidrotic ectodermal dysplasia. Moreover, sustained Ca2+ entry through the channels leads to a range of systemic disorders, including acute pancreatitis, asthma and inflammatory bowel disease. In this review, we describe how aberrant CRAC channel activity causes a range of diseases, highlighting commonalities between these diverse pathologies.
Journal article
2025-06-30T00:00:00+00:00
53
627 - 642
15
CRAC channels, calcium signaling, channelopathy, disease, Humans, Calcium Release Activated Calcium Channels, Animals, ORAI1 Protein, Stromal Interaction Molecule 1, Calcium Signaling, Calcium, Mutation, Neoplasm Proteins, Asthma